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Road traffic state estimation is an essential component of intelligent transportation systems (ITSs). However, road traffic state data collected by traffic detectors are often incomplete, which can cause problems across a variety of transportation applications, such as traffic state prediction and pattern recognition. We present GA-GAN (Graph Aggregate Generative Adversarial Network), consisting of graph sample and aggregate (GraphSAGE) and a generative adversarial network (GAN), to impute missing road traffic state data. Instead of using the original road network structure, which presents the spatial information to process a graph operation, we reconstruct the road network according to the correlation coefficients of road historical data. We utilize GraphSAGE to aggregate the temporal-spatial information from the neighbors of each road in the reconstructed road network. GAN is used to generate complete traffic state data from the extracted temporal-spatial information to achieve traffic state data imputation. To illustrate the efficient performance of the model, experiments are conducted on traffic data collected from California and Seattle, Washington, showing that the proposed model outperforms state-of-the-art methods.

Theoretical analysis revealed LiMn2O4 with F-doping improves the voltage of lithium-ion batteries and retards its capacity decay via reducing the lattice oxygen loss.

Background This study aimed to develop a radiogenomic prognostic prediction model for colorectal cancer (CRC) by investigating the biological and clinical relevance of intratumoural heterogeneity. Methods This retrospective multi-cohort study was conducted in three steps. First, we identified genomic subclones using unsupervised deconvolution analysis. Second, we established radiogenomic signatures to link radiomic features with prognostic subclone compositions in an independent radiogenomic dataset containing matched imaging and gene expression data. Finally, the prognostic value of the identified radiogenomic signatures was validated using two testing datasets containing imaging and survival information collected from separate medical centres. Results This multi-institutional retrospective study included 1601 patients (714 females and 887 males; mean age, 65 years ± 14 [standard deviation]) with CRC from 5 datasets. Molecular heterogeneity was identified using unsupervised deconvolution analysis of gene expression data. The relative prevalence of the two subclones associated with cell cycle and extracellular matrix pathways identified patients with significantly different survival outcomes. A radiogenomic signature-based predictive model significantly stratified patients into high- and low-risk groups with disparate disease-free survival (HR = 1.74, P = 0.003). Radiogenomic signatures were revealed as an independent predictive factor for CRC by multivariable analysis (HR = 1.59, 95% CI:1.03–2.45, P = 0.034). Functional analysis demonstrated that the 11 radiogenomic signatures were predominantly associated with extracellular matrix and immune-related pathways. Conclusions The identified radiogenomic signatures might be a surrogate for genomic signatures and could complement the current prognostic strategies.

Two-dimensional (2D) a-plane gallium nitride, a non-layered 2D material, has promising applications in photoelectric nanodevices due to its direct band bandgap. Herein, employing molecular dynamics simulations, we studied the thermal transport properties of a-plane trilayer GaN, and the temperature, together with strain modulation on the thermal conductivity of the system. The a-plane trilayer GaN shows anisotropic thermal conductivity with 70.22 Wm−1K−1 and 41.81 Wm−1K−1 along zigzag- and armchair- directions respectively at room temperature when extrapolated to infinite size. In addition, the thermal conductivity of trilayer GaN exhibits decreasing trend in response to the increase of temperature. The thermal conductivity decreases monotonically with the increased compressive uniaxial and biaxial strain, while it shows an up-then-down trend under tensile strain. The tunability of thermal conductivity under biaxial strain is much larger than that of uniaxial strain. The phonon density of states is further investigated to understand the behavior of thermal conductivity. The tunability of the system thermal conductivity will expand its applications in thermal management and nanodevices.

Hollow nanoboxes structure have raised great attention as microwave absorption materials on account of their ultralow density and large specific area. By introducing an adjustable interior cavity structure, the dielectric loss and microwave absorption performance were affected by the tunable complex permittivity and impedance matching was improved. In our study, hollow CoS

Background Improved understanding of the stemness regulation mechanism in intrahepatic cholangiocarcinoma (ICC) could identify targets and guidance for adjuvant transarterial chemoembolization (TACE). Methods TCGA database was excavated to identify the ICC stemness-associated genes. The pro-stemness effect of target genes was further analyzed by sphere formation assay, qRT-PCR, western blot, flow cytometric analysis, IHC, CCK8 assay and metabolomic analysis. Based on multivariate analysis, a nomogram for ICC patients with adjuvant TACE was established and our result was further confirmed by a validation cohort. Finally, the effect of dietary methionine intervention on chemotherapy was estimated by in vivo experiment and clinical data. Results In this study, we identified four ICC stemness-associated genes (SDHAF2, MRPS34, MRPL11, and COX8A) that are significantly upregulated in ICC tissues and negatively associated with clinical outcome. Functional studies indicated that these 4-key-genes are associated with self-renewal ability of ICC and transgenic expression of these 4-key-genes could enhance chemoresistance of cholangiocarcinoma cells. Mechanistically, the 4-key-genes-mediated pro-stemness requires the activation of methionine cycle, and their promotion on ICC stemness characteristic is dependent on MAT2A. Importantly, we established a novel nomogram to evaluate the effectiveness of TACE for ICC patients. Further dietary methionine intervene studies indicated that patients with adjuvant TACE might benefit from dietary methionine restriction if they have a relatively high nomogram score (≥ 135). Conclusions Our results show that four ICC stemness-associated genes could serve as novel biomarkers in predicting ICC patient’s response to adjuvant TACE and their pro-stemness ability may be attributed to the activation of the methionine cycle.

It has been well documented that social isolation stress (SIS) can induce posttraumatic stress disorder (PTSD)-like behavior in rodents, however, the underlying mechanism is remained misunderstood. In the current study, we aimed to elucidate the role of NO/NMDAR pathway in PTSD-like behavior through modulating of astrocyte activity and improvement of oxidative stress.Male NMRI mice were used to evaluate the memory function by using Morris water maze (MWM) and fear memory extinction by using freezing response. We used MK-801 (NMDAR-antagonist), L-NNA (NOS-inhibitor), NMDA (NMDAR-agonist), and L-arginine (NO-agent) to find a proper treatment. Also, immunohistochemistry, RT-PCR, and oxidative stress assays were used to evaluate the levels of astrocytes and oxidative stress. We used five mice in each experimental task.Our results revealed that SIS could induce learning and memory dysfunction as well as impairment of fear memory extinction in MWM and freezing response tests, respectively. Also, we observed that combined treatment including blockage of NOS (by L-NNA, 0.5 mg/kg) and NMDAR (by MK-801, 0.001 mg/kg) at subeffective doses could result in improvement of both memory and fear memory. In addition, we observed that SIS significantly increases the GFAP expression and astrocyte activity, which results in significant imbalance in oxidative stress. Coadministration of MK-801 and L-NNA at subeffective doses not only decreases the expression of GFAP, but also regulates the oxidative stress imbalance CONCLUSION: Based on these results, it could be hypothesized that blockage of NO/NMDAR pathway might be a novel treatment for PTSD-like behavior in animals by inhibiting the astrocyte and regulating oxidative stress level.

The rational design on the morphology and microstructure of magnetic carbon-based composites can enhance microwave absorption performance. Herein, a novel hierarchical CoNi@NC hollow microspheres have been successfully synthesized, involving the fabrication of hierarchical CoNi-based carbonate hydroxide hollow microspheres self-assembled by nanosheets using CoNi-glycerate microspheres as self-template, the uniform coating of a layer of polydopamine (PDA) on the surface, and the calcination process at different temperatures. Importantly, the calcination temperature can significantly influence the morphology, microstructures, and microwave absorption performance. All CoNi-based carbonate hydroxide nanosheets coated with PDA can be successfully converted into abundant small CoNi nanoparticles embedded into carbon layer without the agglomeration of CoNi alloys when the calcination temperature is 700 °C. The CoNi@NC-700 sample exhibits outstanding microwave absorption ability especially in X band thanks to optimized impedance matching and enhanced attenuation ability. The RLmin can reach − 69.58 dB at 10.09 GHz with a matching thickness of 2.99 mm, and the effective absorption bandwidth (EAB) is 4.5 GHz (7.97–12.47 GHz) at 3.08 mm, covering the whole X band. Moreover, the broadest EAB is 5.3 GHz (12.7–18 GHz) at 2.13 mm. We believe that this research will provide a new thought to enhance the microwave absorption capability.

Two-dimensional (2D) gallium nitride (GaN) has attracted a lot of attention due to its promising applications in photoelectric nano-devices. Most previous research studies have focused on polar c-plane 2D structures. Here, by employing first principles calculations, we systematically investigate the structural and electronic properties of non-polar m-plane GaN with different numbers of atomic layers. The results show a layer-dependent structure transition and electronic band variation for m-plane GaN. It is found that the monolayer keeps a planar hexagonal structure due to sp2 hybridization, whereas the multilayers are formed by stacking of buckled hexagonal monolayers with unsaturated coordination number at the surface sublayer and bulk-like inner layers. These discrepancies in the structure further induce an indirect to direct transition of the band gap type when the layer number reaches twelve. By carefully examining the relationship between the structure and electronic bandgap, we find that the indirect bandgap comes from the unsaturated surface with a planar like structure. On surface modification, saturation of the surface dangling bonds results in an indirect to direct band gap transition.

Background Notch signaling is highly conserved and critically involved in cell differentiation, immunity, and survival. Activation of the Notch pathway modulates immune cell functions during the inflammatory response. However, it remains unknown whether and how the macrophage Notch1 may control the innate immune signaling TAK1, and RIPK3-mediated hepatocyte necroptosis in liver ischemia and reperfusion injury (IRI). This study investigated the molecular mechanisms of macrophage Notch1 in modulating TAK1-mediated innate immune responses and RIPK3 functions in liver IRI. Methods Myeloid-specific Notch1 knockout (Notch1M−KO) and floxed Notch1 (Notch1FL/FL) mice (n = 6/group) were subjected to 90 min partial liver warm ischemia followed by 6 h of reperfusion. In a parallel in vitro study, bone marrow-derived macrophages (BMMs) were isolated from these conditional knockout mice and transfected with CRISPR/Cas9-mediated β-catenin knockout (KO) vector followed by LPS (100 ng/ml) stimulation. Results IR stress-induced Notch1 activation evidenced by increased nuclear Notch intracellular domain (NICD) expression in liver macrophages. Myeloid Notch1 deficiency exacerbated IR-induced liver damage, with increased serum ALT levels, macrophage/neutrophil accumulation, and proinflammatory cytokines/chemokines production compared to the Notch1FL/FL controls. Unlike in the Notch1FL/FL controls, Notch1M−KO enhanced TRAF6, TAK1, NF-κB, RIPK3, and MLKL but reduced β-catenin activation in ischemic livers. However, adoptive transfer of lentivirus β-catenin-modified macrophages markedly improved liver function with reduced TRAF6, p-TAK1, RIPK3 and p-MLKL in IR-challenged livers. Moreover, disruption of RIPK3 in Notch1M−KO mice with an in vivo mannose-mediated RIPK3 siRNA delivery system diminished IR-triggered hepatocyte death. In vitro studies showed that macrophage NICD and β-catenin co-localized in the nucleus, whereby β-catenin interacted with NICD in response to LPS stimulation. Disruption of β-catenin with a CRISPR/Cas9-mediated β-catenin KO in Notch1FL/FL macrophage augmented TRAF6 activation leading to enhanced TAK1 function. While CRISPR/Cas9-mediated TRAF6 KO in Notch1M−KO macrophage inhibited RIPK3-mediated hepatocyte necroptosis after co-culture with primary hepatocytes. Conclusions Macrophage Notch1 controls TAK1-mediated innate immune responses and RIPK3-mediated hepatocyte necroptosis through activation of β-catenin. β-catenin is required for the macrophage Notch1-mediated immune regulation in liver IRI. Our findings demonstrate that the macrophage Notch1-β-catenin axis is a crucial regulatory mechanism in IR-triggered liver inflammation and provide novel therapeutic potential in organ IRI and transplant recipients.

Using a co-precipitation approach, we introduce Co into LiNi0.5Mn1.5O4 to prepare a series of Co-doped cathode materials in which the Co substitutes partial Ni and Mn. We then systematically study the effects of Co doping at these various sites. The structural and electrochemical properties are investigated by means of X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett–Teller analysis, galvanostatic charge–discharge tests, and electrochemical impedance spectroscopy. The Co-doped samples experience a slight capacity loss, but their cycling stability and rate properties are significantly improved. When Ni and Mn are simultaneously substituted, the capacities at 0.1 C and 2.0 C of a battery using this doped material as the cathode stay at 99.7% and 96.8%, respectively, after 80 cycles, which is much better than the results for a battery with undoped material as the cathode.

We report the transition of a strain-induced centrosymmetric β-phase to a non-centrosymmetric α-phase for monolayer tellurene based on density functional theory calculations. The phase transition is represented by the displacement of the middle-layer Te atoms from the center of the unit cell in the y-direction. The critical point for the phase transition is found to be at 0.5% biaxial tensile strain. By analyzing the bond variation and the phonon spectra, we attribute the phase transition to the decrease of the bonding strength at the tensile strain and the atom migration corresponding to the phonon vibration mode along the distorted direction. The transition to the α-phase under strain is further confirmed from the calculated electronic band structure where the spin–orbit coupling (SOC) induces a large Rashba splitting due to symmetry breaking, which may enable the control of spin via the electric field. Two-dimensional ferroelectrics can be formed upon transition of the strain-induced β-phase to the α-phase, and a high polarization of about 90 μC cm−2 can be achieved via a tensile strain, giving rise to a giant piezoelectric coefficient that is two orders of magnitude higher than that of the MoS2 monolayer.

Organic electrodes for rechargeable devices have attracted tremendous attention as a promising alternative in lithium-ion batteries (LIBs). Unfortunately, most of the reported organic anodes face huge challenges in practical application because of the low reversible specific capacity, poor rate performance, and short cycling life. Herein, we facilely chelated the renewable tannic acid (TA) via ferric ions and generated a novel organic anode material (TA-Fe) using in LIBs for the first time. Benefiting from the chelation between ferric ions and catechol groups, which changes the inherent microstructure of TA and inhibits its dissolution in electrolyte, the TA-Fe anodes exhibit outstanding electrochemical performance including high reversible capacity (1016 mAh/g at 0.1 A/g), excellent rate capability, and ultra-long cycling stability (10.0 A/g over 16000 cycles with a capacity retention of 78.8%). Besides presenting a high-performance organic electrode, we expect this work to inspire the preparation of other organic materials for advanced LIBs.

The indirect bandgap of two-dimensional GaN hinders its application in the optical field. Hydrogenation can convert the bandgap type of the GaN monolayer from an indirect to a direct one and also tune the bandgap size. The thermal transport, an important property in the application of two-dimensional materials, is also influenced by hydrogenation. By performing first-principles calculations and solving the phonon Boltzmann equation, we investigate the effect of hydrogenation on the thermal conductivity of the GaN monolayer. The results show that hydrogenation will slightly increase the thermal conductivity of the GaN monolayer from 70.62 Wm−1 K−1 to 76.23 Wm−1 K−1 at 300 K. The little effect of hydrogenation on thermal conductivity is mainly dominated by two competing factors: (1) the reduction of ZA mode lifetime due to the breaking of reflection symmetry after hydrogenation and (2) the increased contribution from TA and LA modes due to the reduction of anharmonic scattering caused by the enlarged phonon bandgap after hydrogenation. The results are compared with other two-dimensional materials with hexagonal monolayer structures.

Background and aims Epidemiological studies have shown direct associations between type 2 diabetes and the risk of cancers. Accumulating evidence indicates that metformin is profoundly implicated in preventing tumor development. However, the exact mechanism underlying the anti-tumor effects of metformin in hepatocellular carcinoma (HCC) is still not clear. Methods In this study, we investigated the effects of metformin on a mouse hepatocellular carcinoma (HCC) model and interleukin-22 (IL-22)-associated carcinogenesis in vitro. Results We found that metformin significantly suppressed the incidence and tumor burden of HCC in the diethyl-nitrosamine (DEN)-induced HCC mouse model. As expected, the expression of IL-22, an important factor involved in HCC progression, was markedly reduced by metformin. Treatment of HCC cells with metformin inhibited IL-22 induced cell proliferation, migration and invasion, and promoted cell apoptosis. Furthermore, ectopic expression of IL-22 makes HCC more aggressive whereas metformin largely compromised it in vitro and in vivo. Mechanistically, the whole transcriptome analysis and functional analysis revealed that Hippo signaling pathway was involved in the anti-tumor ability of metformin. Consistent with this, metformin directly inhibited LATS1/2 and activated Mst1/2, phosphorylated YAP1 in vitro. After blocking the Hippo pathway by XMU-MP-1, the inhibitor of MST1/2, the inhibitory effects by metformin were dramatically attenuated as shown by in vitro study. Conclusions Collectively, our findings illuminate a new regulatory mechanism, metformin activates Hippo signaling pathway to regulate IL-22 mediated HCC progression and provide new insights into its tumor-suppressive roles.

Foxo1 transcription factor is an evolutionarily conserved regulator of cell metabolism, oxidative stress, inflammation, and apoptosis. Activation of Hedgehog/Gli signaling is known to regulate cell growth, differentiation, and immune function. However, the molecular mechanisms by which interactive cell signaling networks restrain oxidative stress response and necroptosis are still poorly understood. Here, we report that myeloid-specific Foxo1 knockout (Foxo1M-KO) mice were resistant to oxidative stress-induced hepatocellular damage with reduced macrophage/neutrophil infiltration, and proinflammatory mediators in liver ischemia/reperfusion injury (IRI). Foxo1M-KO enhanced β-catenin-mediated Gli1/Snail activity, and reduced receptor-interacting protein kinase 3 (RIPK3) and NIMA-related kinase 7 (NEK7)/NLRP3 expression in IR-stressed livers. Disruption of Gli1 in Foxo1M-KO livers deteriorated liver function, diminished Snail, and augmented RIPK3 and NEK7/NLRP3. Mechanistically, macrophage Foxo1 and β-catenin colocalized in the nucleus, whereby the Foxo1 competed with T-cell factor (TCF) for interaction with β-catenin under inflammatory conditions. Disruption of the Foxo1–β-catenin axis by Foxo1 deletion enhanced β-catenin/TCF binding, activated Gli1/Snail signaling, leading to inhibited RIPK3 and NEK7/NLRP3. Furthermore, macrophage Gli1 or Snail knockout activated RIPK3 and increased hepatocyte necroptosis, while macrophage RIPK3 ablation diminished NEK7/NLRP3-driven inflammatory response. Our findings underscore a novel molecular mechanism of the myeloid Foxo1–β-catenin axis in regulating Hedgehog/Gli1 function that is key in oxidative stress-induced liver inflammation and necroptosis.

Notch signaling plays important roles in the regulation of immune cell functioning during the inflammatory response. Activation of the innate immune signaling receptor NLRP3 promotes inflammation in injured tissue. However, it remains unknown whether Jagged1 (JAG1)-mediated myeloid Notch1 signaling regulates NLRP3 function in acute liver injury. Here, we report that myeloid Notch1 signaling regulates the NLRP3-driven inflammatory response in ischemia/reperfusion (IR)-induced liver injury. In a mouse model of liver IR injury, Notch1-proficient (Notch1FL/FL) mice receiving recombinant JAG1 showed a reduction in IR-induced liver injury and increased Notch intracellular domain (NICD) and heat shock transcription factor 1 (HSF1) expression, whereas myeloid-specific Notch1 knockout (Notch1M-KO) aggravated hepatocellular damage even with concomitant JAG1 treatment. Compared to JAG1-treated Notch1FL/FL controls, Notch1M-KO mice showed diminished HSF1 and Snail activity but augmented NLRP3/caspase-1 activity in ischemic liver. The disruption of HSF1 reduced Snail activation and enhanced NLRP3 activation, while the adoptive transfer of HSF1-expressing macrophages to Notch1M-KO mice augmented Snail activation and mitigated IR-triggered liver inflammation. Moreover, the knockdown of Snail in JAG1-treated Notch1FL/FL livers worsened hepatocellular functioning, reduced TRX1 expression and increased TXNIP/NLRP3 expression. Ablation of myeloid Notch1 or Snail increased ASK1 activation and hepatocellular apoptosis, whereas the activation of Snail increased TRX1 expression and reduced TXNIP, NLRP3/caspase-1, and ROS production. Our findings demonstrated that JAG1-mediated myeloid Notch1 signaling promotes HSF1 and Snail activation, which in turn inhibits NLRP3 function and hepatocellular apoptosis leading to the alleviation of IR-induced liver injury. Hence, the Notch1/HSF1/Snail signaling axis represents a novel regulator of and a potential therapeutic target for liver inflammatory injury.